All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells.

Leukemia inhibitory factor (LIF) is prevalently expressed in human medulloblastomas in vivo and in vitro. Blockage of LIF expression or biological function can inhibit in vitro growth and induce differentiation-like phenotypes of medulloblastoma cells (Med-3), suggesting a redifferentiation potential of Med-3 cells when intrinsic dedifferentiation factor(s) is suppressed or external differentiation element(s) is exerted. All-trans retinoic acid (RA) can induce differentiation in some types of cancers but its effect on medulloblastoma cells has not yet been described. To address the above issues, three dosages (5, 8 and 10 mumol/L) of RA were used to treat Med-3 cells and their effects on the target cells were evaluated by multiple approaches. It was found that, in addition to induction of morphological changes and growth inhibition, RA could repress LIF expression as well as the telomerase activity of Med-3 cells in time- and dose-related fashions. Our data thus suggest that the growth inhibitory effect of RA on Med-3 cells may be correlated with the LIF down-regulation. Reduction of telomerase activity by RA indicates that this enzymatic activity is a potential differentiation indicator of medulloblastoma cells.